Dr. Joe W. Gray, a physicist and an engineer by training, holds positions as professor and Gordon Moore Endowed Chair of the Department of Biomedical Engineering; director of the Center for Spatial Systems Biomedicine; and associate director for Biophysical Oncology in the Knight Cancer Institute at Oregon Health & Science University. He is also professor emeritus, University of California San Francisco. Currently, he is a principal investigator of an NCI Cancer Systems Biology Consortium center, an NIH Library of Integrated Network-based Cellular Signatures (LINCS) center, and an NCI Human Tumor Atlas Network Research center; and he is co-director of OHSU’s Serial Measurement of Molecular and Architectural Responses to Therapy (SMMART) program.

Prior to joining OHSU, he was a staff scientist in the biomedical sciences division of the Lawrence Livermore National Laboratory (1972-1991); professor of laboratory medicine at the University of California, San Francisco (1991-2011); and associate laboratory director for biosciences and director of life sciences at the Lawrence Berkeley National Laboratory (2003-2011).

Currently, he is the PI of the NCI/Cancer Systems Biology Consortium Measuring, Modeling and Controlling Heterogeneity (M2CH) center, which aims to develop a systems-level understanding of how intrinsic and extrinsic factors work together to enable triple-negative breast cancer to escape therapeutic control and devise robust control strategies. He also is PI of an NIH Library of Integrated Network-based Cellular Signatures program (LINCS) center that aims to develop a dataset and computational strategy to elucidate how microenvironmental signals affect cell intrinsic intracellular transcriptional- and protein-defined molecular networks to generate experimentally observable phenotypes. Dr. Gray also co-directs the Serial Measurement of Molecular and Architectural Responses to Therapy (SMMART) clinical trials program that focuses on identifying mechanisms by which advanced individual cancers of the breast, prostate, pancreas and AML become resistant to treatment to better treat the individual cancers.

Dr. Gray's work is described in over 500 publications and 80 US patents. He is a Fellow of the American Association for the Advancement of Science, the American Institute for Medical and Biological Engineering and a member of the National Academy of Medicine. He serves as the Executive Councilor of the Board of Councilors for the Radiation Effects Research Foundation (RERF), Hiroshima, Japan.

Major awards include the Radiation Research Society Research Award (1985), the E.O. Lawrence Award, United States Department of Energy (1986); Curt Stern Award, American Society for Human Genetics (2001); Honorary Doctorate, University of Tampere, Finland (2005); Brinker Award for Scientific Distinction, Susan G. Komen^® Foundation (2007); Team Science Award, American Association for Cancer Research (2008); the Fulwyler Award, International Society for the Advancement of Cytometry (2010); the William L. McGuire Memorial Lecture Award, AACR San Antonio Breast Cancer Conference (2011) ; Lawrence Livermore National Laboratory Entrepreneur's Hall of Fame Honoree (2012); Simon M. Shubitz Award from the University of Chicago (2012); an Honorary Doctorate of Engineering, Colorado School of Mines (2012); the 18th Annual Alfred G. Knudson Award Lecture in Cancer Genetics (2014) and Fellow, American Association of Cancer Research Academy Class of 2016.

Dr. Gray’s early scientific contributions involved development of flow cytometric techniques for cell and genome analysis. These included techniques for high-speed chromosome sorting, and BrdUrd/DNA analysis of cell proliferation. Sorter-purified chromosomes were cloned to produce chromosome-specific DNA libraries that were distributed worldwide and were used to assemble early chromosome maps in the human genome project. Aspects of high speed sorting developed in the Gray Lab are now incorporated in all modern sorters. BrdUrd/DNA analysis has become a standard technique for assessment of cell proliferation.

The availability of chromosome specific libraries inspired the Gray and Pinkel laboratories to develop fluorescence in situ hybridization (FISH) to stain specific chromosome regions. FISH dramatically simplified metaphase chromosome classification and enabled detection of numerical and structural aberrations in interphase cells. Dr. Gray and Dr. Daniel Pinkel’s papers describe the first uses of FISH for gene amplification (specifically ERBB2), gene deletion (specifically RB1) and translocation (specifically BCR-ABL) in clinical samples. FISH has been licensed to Abbott Diagnostics and is now used worldwide for disease diagnosis, molecular assessment of chromosome abnormalities and analysis of the organization of interphase nuclei.

Experience with FISH led the Gray, Pinkel and collaborating laboratories to the invention of comparative genomic hybridization (CGH) for genome-wide assessment of copy number abnormalities. CGH enabled interpretation of previously intractable complex cancer genomes by mapping the aberrations onto representations of normal genomes. These studies inspired Gray and Collins laboratories to develop a genome sequencing-based approach to assessment of copy number and genome structure abnormalities called End Sequence Profiling (ESP). ESP was based on mapping sequences from the ends of clones from tumor libraries onto a normal representation of the normal genome. This approach is now the basis for paired end sequencing applications implemented using massively parallel sequencing.

Applications of these approaches to human and model cancers revealed the remarkable genomic complexity that characterizes most solid tumors and demonstrated the presence of recurrent genome aberrations in a broad range of human cancers.  In particular, they showed that human breast cancers pass through telomere crisis and become immortal during progression from usual ductal hyperplasia to carcinoma in situ. This is important since it suggests strategies to prevent this critical transition. Integrated analyses of omic data led to identification of molecular signatures that predicted disease progression and response to treatment.

The Gray Lab now focuses on the application of spatial systems biology approaches to elucidate tumor intrinsic and extrinsic mechanisms that enable cancer progression and/or that determine therapeutic responses. The OHSU Center for Spatial Systems Biology seeks to elucidate how genomic and epigenomic events influence the few Ǻngström to millimeter scale structures that enable function in cells and tissues.